title: A combined anatomic and electrophysiologic substrate based approach for sudden cardiac death risk stratification.
abstract: BACKGROUND
  Although left ventricular ejection fraction (LVEF) is the primary determinant for sudden cardiac death (SCD) risk stratification, in isolation, LVEF is a sub-optimal risk stratifier. We assessed whether a multi-marker strategy would provide more robust SCD risk stratification than LVEF alone.
  
  
  METHODS
  We collected patient-level data (n = 3355) from 6 studies assessing the prognostic utility of microvolt T-wave alternans (MTWA) testing. Two thirds of the group was used for derivation (n = 2242) and one-third for validation (n = 1113). The discriminative capacity of the multivariable model was assessed using the area under the receiver-operating characteristic curve (c-index). The primary endpoint was SCD at 24 months.
  
  
  RESULTS
  In the derivation cohort, 59 patients experienced SCD by 24 months. Stepwise selection suggested that a model based on 3 parameters (LVEF, coronary artery disease and MTWA status) provided optimal SCD risk prediction. In the derivation cohort, the c-index of the model was 0.817, which was significantly better than LVEF used as a single variable (0.637, P < .001). In the validation cohort, 36 patients experienced SCD by 24 months. The c-index of the model for predicting the primary endpoint was again significantly better than LVEF alone (0.774 vs 0.671, P = .020).
  
  
  CONCLUSIONS
  A multivariable model based on presence of coronary artery disease, LVEF and MTWA status provides significantly more robust SCD risk prediction than LVEF as a single risk marker. These findings suggest that multi-marker strategies based on different aspects of the electro-anatomic substrate may be capable of improving primary prevention implantable cardioverter-defibrillator treatment algorithms.
authors.affiliation: Cardiology Division, Emory University School of Medicine, Atlanta, GA; Cardiology Division, Massachusetts General Hospital, Boston, MA.
authors.forename: Faisal M
authors.initials: FM
authors.lastname: Merchant
authors.forename: Hui
authors.initials: H
authors.lastname: Zheng
authors.forename: Thomas
authors.initials: T
authors.lastname: Bigger
authors.forename: Richard
authors.initials: R
authors.lastname: Steinman
authors.forename: Takanori
authors.initials: T
authors.lastname: Ikeda
authors.forename: Roberto F E
authors.initials: RF
authors.lastname: Pedretti
authors.forename: Jorge A
authors.initials: JA
authors.lastname: Salerno-Uriarte
authors.forename: Catherine
authors.initials: C
authors.lastname: Klersy
authors.forename: Paul S
authors.initials: PS
authors.lastname: Chan
authors.forename: Cheryl
authors.initials: C
authors.lastname: Bartone
authors.forename: Stefan H
authors.initials: SH
authors.lastname: Hohnloser
authors.forename: Jeremy N
authors.initials: JN
authors.lastname: Ruskin
authors.forename: Antonis A
authors.initials: AA
authors.lastname: Armoundas
mesh_terms: D016757:Death, Sudden, Cardiac / Q000453:epidemiology / Q000209:etiology / Q000517:prevention & control; D017147:Defibrillators, Implantable; D022062:Electrophysiologic Techniques, Cardiac; D006801:Humans; D011322:Primary Prevention; D018570:Risk Assessment / Q000379:methods*; D017180:Tachycardia, Ventricular / Q000150:complications / Q000401:mortality / Q000628:therapy*